Biology subjects

Das, J. K.

Publications and source records attributed to Das, J. K..

5 recordsLinked to original sources

bioRxiv2026

A Synthetic Microbial Therapy Rewires Antitumor Immunity Across Multiple Cancer Types

Microbial immunotherapies show promise against cancer, yet broad efficacy and mechanistic insight remain elusive. Here, we introduce SPIKE 1.0 (S1.0), a metabolically engineered bacterium that converts tryptophan into immunomodulatory hydroxyindoles via tryptophan monooxygenase to remodel the tumor microenvironment (TME). A single systemic dose of S1.0 elicited potent, durable antitumor responses across multiple murine models, including humanized mice, with minimal toxicity. S1.0 enhanced inflammatory signaling, activated innate and adaptive immunity, and promoted T cell persistence, memory, and resistance to exhaustion. It outperformed checkpoint inhibitors and synergized with chemotherapy. Multi-omics profiling revealed that S1.0 rewired amino acid metabolism in tumor-infiltrating immune cells and disrupted immunosuppressive networks. These results establish S1.0 as a scalable, cost-effective microbial immunotherapy with broad translational potential for solid tumors.

immunology↗

bioRxiv2022

A metabolically engineered bacterium controls autoimmunity by remodeling the pro-inflammatory microenvironment

Immunotherapy has led to impressive advances in the treatment of autoimmune and pro-inflammatory disorders; yet, its clinical outcomes remain limited by a variety of factors including the pro-inflammatory microenvironment (IME). Discovering effective immunomodulatory agents, and the mechanisms by which they control disease, will lead to innovative strategies for enhancing the effectiveness of current immunotherapeutic approaches. We have metabolically engineered an attenuated bacterial strain (i.e., Brucella melitensis 16M {Delta}vjbR, Bm{Delta}vjbR) to produce indole, a tryptophan metabolite that controls the fate and function of regulatory T cells (Tregs). We demonstrated that treatment with this strain polarized M2 macrophages (M{varphi}) which produced anti-inflammatory cytokines (e.g., IL-10) and promoted Treg function; moreover, when combined with adoptive cell transfer (ACT) of Tregs, a single treatment with our engineered bacterial strain dramatically reduced the incidence and score of autoimmune arthritis and decreased joint damage. These findings show how a metabolically engineered bacterium can constitute a powerful vehicle for improving the efficacy of immunotherapy, defeating autoimmunity and reducing inflammation by remodeling the IME and augmenting Treg function.

immunology↗

bioRxiv2020

A Numerical Representation and Classification of Codons to Investigate Codon Alternation Patterns during Genetic Mutations on Disease Pathogenesis

Alteration of amino acids is possible due to mutation in codons that could have potential reasons to occur disease. Single nucleotide substitutions (SNS) in genetic codon thus have prime importance for their ability to occur mutations that may be deleterious indeed. Effective mutation analysis can help to predict the fate of the diseased individual which can be validated later by in-vitro experiments. Hence in this present study, we try to investigate the codon alteration patterns and their impact during mutation for the genes known to be responsible for a particular disease. We use a numerical representation of four nucleotides based on the number of hydrogen bonds in their chemical structures and make a classification of 64 codons as well as corresponding 20 amino acids into three different classes (Strong, Weak and Transitional). The entire analysis has been carried out based on these classifications. For our current study, we consider two neurodegenerative diseases, Parkinsons disease, and Glaucoma. Several evidences claim similarities between both the diseases but proper pathogenetic factors are still unknown. The analysis reveals that the strong class of codons is highly mutated followed by the weak and transitional class. We observe that most of the mutations occur in the first or second positions in the codon rather than the third and mutations that occurred at the second place of codons are majorly deleterious. In most cases, the change in the determinative degree of codon due to mutation is directly proportional to the physical density property. Furthermore, we derive a determinative degree of five wild-type amino acid sequences, which can help biologists to understand the evolutionary relationship among them based on amino acid occurrence frequencies in proteins. In this regard we proposed an alignment-free method SSADDA (Sequence Similarity Analysis using Determinative Degree of Amino acid). Thus, our scheme gives a more microscopic and alternative representation of the existing codon table that helps in deciphering interesting codon alteration patterns during mutations in disease pathogenesis.

bioinformatics↗

bioRxiv2018

The variations of human miRNAs and Ising like base pairing models

miRNAs are small about 22-base pair long, RNA molecules are of extreme biological importance. Like other longer RNA molecules, messages in miRNAs are encoded by the permutations of only four nucleotide bases represented by A, U, C and G. However, just like words in any language, not all combination of these alphabets make a meaningful word. In fact, we find that the distributions of nucleotides bases in human miRNAs show significant deviation from randomness. First, a miRNA sequence containing four bases are mapped into a binary string with three kinds of classifications according to their chemical properties. Then, we propose a simple nearest neighbor model (Ising model) to understand the statistical variations in human miRNAs.

bioinformatics↗

bioRxiv2017

Distribution of Purines and Pyrimidines over miRNAs of Human, Gorilla and Chimpanzee

Meaningful words in English need vowels to break up the sounds that consonants make. The Nature has encoded her messages in RNA molecules using only four alphabets A, U, C and G in which the nine member double-ring bases (adenine (A) and Guanine (G)) are purines, while the six member single-ring bases (cytosine (C) and uracil (U)) are pyrimidines. Four bases A, U, C and G of RNA sequences are divided into three kinds of classifications according to their chemical properties. One of the three classifications, the purine-pyrimidine class is important. In understanding the distribution (organization) of purines and pyrimidines over some of the non-coding regions of RNA, all miRNAs from three species of Family Hominidae (namely human, gorilla and chimpanzee) are considered. The distribution of purines and pyrimidines over miRNA shows deviation from randomness. Based on the quantitative metrics (fractal dimension, Hurst exponent, Hamming distance, distance pattern of purine-pyrimidine, purine-pyrimidine frequency distribution and Shannon entropy) five different clusters have been made. It is identified that there exists only one miRNA in human hsa-miR-6124 which is purely made of purine bases only.\n\nAMS Subject Classification: 92B05 & 92B15

bioinformatics↗